Principles of Fungal Infection Diagnosis and Treatment in Children

2. Principles of Fungal Diagnosis and Treatment
Presented by
Marwa Alsaid Ahmed

3. Introduction
There are approximately 1.5 million different species of fungi
on Earth, but only about 300 of those are known to infect
human
• Fungi can be classified into:-
• 1-YEAST
• Which are unicellular and
reproduce by budding
• 2-MOLDS
• Which are multicellular and
reproduce by elongation and
branching
• 3-DIMORPHIC
• can exist as yeast or molds

4. CLASSIFICATION OF FUNGAL INFECTION
Superficial mycoses
• Superficial candidiasis
• Dermatophyte infection
• Pityriasis versicolor
Subcutaneous mycoses
Systemic mycoses

5. Candidiasis
Caused by the yeast Candida.
Candidiasis can occur in the
mouth and throat, vagina, or
the bloodstream.
Aspergillosis
Caused by fungus Aspergillus and
usually occurs in people with lung
diseases or weakened immune
systems
Blastomycosis
Caused by
fungus Blastomyces, which
lives in moist soil in parts of
the United States and Canada.
Histoplasmosis
Caused by Histoplasma, which
lives in the environment, often in
association with bird or bat
droppings.
Coccidioidomycosis (Valley Fever)
Caused by Coccidioides, a soil
organism may present with
chest infection or disseminated
infection of the skin, meninges,
bone or joints.
Mucormycosis
A rare infection that mainly
affects people with weakened
immune systems

6. C. neoformans infection
Caused by Cryptococcus
neoformans, which can infect
the brain (meningitis) in
people with HIV/AIDS.
Pneumocystis pneumonia (PCP)
Caused by the
fungus Pneumocystis
jirovecii and mainly affects
people with weakened immune
systems.
Ringworm
A common fungal skin infection that often looks
like a circular rash.

7. Superficial candidiasis
 Candidal Diaper Dermatitis
• Erythematous papules and pustules
coalescing into a beefy red confluent
painful rash with sharp borders
• Surrounded by small satellite lesions.
• The skin folds are commonly involved
• Treat any diaper rash that has been present for >3 days with
topical antifungal therapy such as nystatin, clotrimazole, or
miconazole. If significant inflammation is present, the
addition of hydrocortisone 1% may be useful for the 1st 1-2
days, but cautiously in infants as it can lead to adverse effects.
Frequent diaper changes and short periods without diapers
are important adjunctive treatments.

8.  ORAL CANDIDIASIS
• Oral thrush is a superficial mucous
membrane infection that affects
approximately 2-5% of normal neonates.
Oral thrush can develop as early as 7-10
days of age.
• The use of antibiotics, especially in the
1st yr of life, can lead to recurrent or
persistent thrush.
• It is characterized by pearly white, curdish material visible on the
tongue, palate, and buccal mucosa.
• Oral thrush may be asymptomatic or can cause pain, fussiness, and
decreased feeding, leading to inadequate nutritional intake and
dehydration.
• The most commonly prescribed antifungal agent is nystatin

9.  VULVOVAGINITIS
• Vulvovaginitis is a common Candida infection of pubertal and
postpubertal female patients . Predisposing factors include
pregnancy, use of oral contraceptives, diabetes mellitus ,and use of
oral antibiotics.
• Clinical manifestations can include pain or itching, dysuria, vulvar or
vaginal erythema, and an opaque white or cheesy exudate.
• treated with either vaginal creams or troches of nystatin,
clotrimazole, or miconazole. Oral therapy with a single dose of
fluconazole is also effective.
 UNGUAL AND PERIUNGUAL INFECTIONS
• Candida onychomycosis differs from tinea infections
by its propensity to involve the fingernails and not the
toe nails, and by the associated paronychia.
Candida paronychia often responds to treatment
consisting of keeping the hands dry and using a
topical antifungal agent.

10. Dermatophyte infection
• Dermatophytosis includes several distinct
clinical entities, depending on the anatomic
site and etiologic agents involved
Tinea Capitis Tinea corporis Tinea pedis Tinea unguium
(onychomycosis)

11. Pityriasis versicolor
• Caused by Malassezia furfur.
• The lesions of tinea versicolor are scaly, oval, hyperpigmented
or hypopigmented macules usually 1 to 2 cm in diameter
located on the upper chest, back, or arms.
• The diagnosis is confirmed by KOH examination of scrapings
from the lesion that show the characteristic "spaghetti and
meatballs" appearance

12. Systemic mycoses

13. Systemic Candida Infections
 Neonatal Infections
• Candida species are the third most common cause of bloodstream
infection in premature infants.
• Significant risk factors for neonatal invasive candidiasis include
prematurity, low birthweight, exposure to broad-spectrum antibiotics,
abdominal surgery, and presence of a central venous catheter.
• Signs of invasive candidiasis among premature infants are often
nonspecific and include temperature instability, lethargy, apnea,
hypotension, respiratory distress, abdominal distention, and
thrombocytopenia. Central nervous system involvement is common and is
most accurately described as meningoencephalitis. Candida infections
involving the central nervous system often result in abscesses leading to
unremarkable cerebrospinal fluid parameters.
• Candidemia is associated with an increased risk of severe retinopathy of
prematurity.

14. • DIAGNOSIS
• Mucocutaneous infections are most often diagnosed by direct clinical exam.
Scrapings of skin lesions may be examined with a microscope after Gram staining or
suspension in KOH.
• Definitive diagnosis of invasive disease requires histologic demonstration of the
fungus in tissue specimens or recovery of the fungus from normally sterile body
fluids.
• Blood culture volumes in infants are often only 0.5-1 mL, making the sensitivity in
this population almost certainly lower.
• Hematologic parameters are sensitive but not specific. Thrombocytopenia occurs in
more than 80% of premature infants with invasive candidiasis.
• PROPHYLAXIS
• NICUs with a high incidence of invasive candidiasis should consider prophylaxis
with fluconazole in infants <1,000 g birthweight. Twiceweekly fluconazole at 3 and
6 mg/kg/dose decreases rates of both colonization with Candida species and
invasive fungal infections
• TREATMENT
• Every attempt should be made to remove or replace central venous catheters.
• Amphotericin B has been the mainstay of therapy for systemic candidiasis.

15. Invasive candidiasis in Immunocompromised
Children and Adolescents
• HIV-Infected Children
• Catheter-Associated Infections
• Cancer and Transplant Patients: Candida and Aspergillus
infections, are a significant problem in oncology patients
with chemotherapy-associated neutropenia. Accordingly,
empirical antifungal therapy should be started if fever and
neutropenia persist for 5 or more days. Fluconazole can
be used if the patient is not critically ill . Amphotericin B
should be used in critically ill patients.
• Voriconazole prophylaxis decreases the incidence of
candidemia in bone marrow transplant recipients with
the additional benefit over fluconazole of mold
prophylaxis.

16. Histoplasmosis
(Histoplasma capsulatum)
 Acute pulmonary histoplasmosis: The prodrome is not specific
and usually consists of flu-like symptoms including headache,
fever, chest pain, cough, and myalgias. Hepatosplenomegaly
occurs more often in infants and young children.
 Symptomatic infections may be associated with significant
respiratory distress and hypoxia and can require intubation,
ventilation, and steroid therapy. Acute pulmonary
disease can also manifest with a prolonged illness
(10 days to 3 wk) consisting of weight loss, dyspnea,
high fever, asthenia, and fatigue. In 10% of patients,
infection is a sarcoid-like disease with arthritis or
arthralgia, erythema nodosum, keratoconjunctivitis, iridocyclitis,
and pericarditis.

17.  In endemic regions, these lesions can mimic parenchymal
tumors. Mediastinal granulomas form when
reactive hilar lymph nodes coalesce
and mat together. Although these lesions
are usually asymptomatic, huge granulomas
can compress the mediastinal structures,
producing symptoms of esophageal,
bronchial, or vena caval obstruction.
 Chronic pulmonary histoplasmosis :
is an opportunistic infection. This entity is rare in children.
 Progressive disseminated histoplasmosis:
Fever is the most common finding and can persist for weeks to
months before the condition is diagnosed. The majority of
patients have hepatosplenomegaly, lymphadenopathy, anemia,
and thrombocytopenia.

18.  DIAGNOSIS
• Histoplasma typically grows within 6 wk on Sabouraud agar at 25°C
• A confirmatory test using a chemiluminescent DNA probe for H. capsulatum is
necessary to establish a definitive identification.
• Detection of fungal polysaccharide antigen by radioimmunoassay is the most
widely available diagnostic study for patients with suspected progressive
disseminated histoplasmosis.
• Skin testing is useful only for epidemiologic studies because cutaneous reactivity
is lifelong
 TREATMENT
• Asymptomatic or mildly symptomatic acute pulmonary histoplasmosis: no
treatment
• Oral itraconazole or fluconazole should be considered in patients with acute
pulmonary infections who fail to improve clinically within 1 mo
• Patients with primary or reexposure pulmonary histoplasmosis who become
hypoxemic or require ventilatory support should receive amphotericin B
• Amphotericin B continues to be the cornerstone of therapy for infants with
progressive disseminated histoplasmosis

19. Aspergillus
 Allergic Disease (Hypersensitivity Syndromes)
• Asthma
• Extrinsic alveolar alveolitis.
• Allergic bronchopulmonary aspergillosis.
• Allergic aspergillus sinusitis.
 Saprophytic (Noninvasive) Syndromes
• Pulmonary aspergilloma.
• Chronic pulmonary aspergillosis.
• Sinusitis
• Otomycosis
 Invasive Disease
In immunocompromized persons affecting eye , CNS , bone or heart

20. DIAGNOSIS
• X-ray and CT CHEST
• Culture :BAL, sputum, tissues
• PCR , Glactomannan antigen
Treatment
• Voriconazole better than amphotericin B
• Growth factors to increase neutrophil counts, granulocyte
transfusions, interferon-γ, and surgery

21. Coccidioidomycosis
Primary Pulmonary Infection
60% 40%
Asymptomatic Infection Symptomatic Infection
(occasional residual pulmonary 75-85% Spontaneous recovery
cavity, nodule) 5-10% Residual pulmonary
disease (cavity or nodule)
5-10% Extrapulmonary
dissemination

22.  Desert rheumatism (valley fever)
• Fever, chest pain,arthralgias (especially
knees and ankles), erythema nodosum and
sometimes erythema multiforme rash
• The chest examination is often normal
even if radiographic findings are present
(hilar and mediastinal lymphadenopathy are common).

23.  DIAGNOSIS
• CBC might show an elevated eosinophil count, and marked eosinophilia can
accompany dissemination
• Culture: sputum ,BAL ,Blood , urine.
• Serology : three major methods are used, including
EIA, complementfixation (CF), and immunodiffusion.
 Treatment
• First-line agents include oral and intravenous preparations
of fluconazole (6-12 mg/kg/day IV or PO) and itraconazole
(5-10 mg/kg/day).
• Amphotericin B is preferred for initial treatment of severe
infections.

24. Zygomycosis
(Mucormycosis)
Sinus and rhinocerebral: the most common, occur primarily
in persons with diabetes mellitus or who are
immunocompromised.
Infection typically originates in the paranasal sinuses.
Initial symptoms are consistent with sinusitis and
include headache, retroorbital pain, fever, and nasal
discharge. Infection can evolve rapidly or be slowly
progressive.
Orbital involvement manifesting as periorbital edema,
proptosis, ptosis, and ophthalmoplegia can occur early in the disease. The
nasal discharge is often dark and bloody; examination of the nasal
mucosa reveals the hallmark finding of black, necrotic areas; however, its
absence does not exclude the diagnosis.

25.  Pulmonary zygomycosis :occurs in severely neutropenic
patients and is characterized by fever, tachypnea, and
productive cough with pleuritic chest pain and hemoptysis.
• A wide range of pulmonary radiologic findings, including
solitary pulmonary nodule, segmental or lobar consolidation,
and cavitary and bronchopneumonic changes, are recognized.
 Gastrointestinal zygomycosis
 Disseminated zygomycosis :is associated with a very high
mortality rate
 Cutaneous and soft tissue zygomycosis: can complicate
burns or surgical wounds.

26.  DIAGNOSIS
• Direct morphologic identification of mycotic elements and
recovery of Zygomycetes in culture
• Serologic tests for detecting zygomycosis are not clinically
useful.

27.  TREATMENT
• All forms of the disease can be aggressive and difficult to treat, with high fatality
rates
• The optimal therapy for zygomycosis in children requires early diagnosis and
prompt institution of medical therapy combined with extensive surgical
debridement of all devitalized tissue, correctionof the underlying disease, if
possible, is an essential component of management
• Use of granulocyte colony-stimulating factor or granulocyte macrophage colony-
stimulating factor to reverse immunosuppression is recommended in conjunction
with antifungal agents
• Amphotericin B deoxycholate (1-1.5 mg/kg/day to a total dose of70 mg/kg or 3-4 g
over several weeks) or amphotericin B lipid complex(3-5 mg/kg/day) has been
successful in treating infection
• Pulmonary and cutaneous disease has been successfullytreated with intermediate
dosages of amphotericin B (30 mg/kgtotal dose)

28. Principles of Antifungal Therapy

29. Antifungal Therapy
ECHINOCANDINS
Anidulafungin
Caspofungin
Micafungin
AZOLES
Clotrimazole
Ketoconazol
Fluconazole
Itraconazole
Posaconazole
Voriconazole
Miconazole
PYRIMIDINE
ANALOGS
5-Fluorocytosine
POLYENES
Amphotericin B
Nystatin